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  • Electronic Resource  (7)
  • insulin  (4)
  • Mammary carcinoma  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 33 (1990), S. 384-386 
    ISSN: 1432-0428
    Keywords: Insulin action profiles ; timing of injection ; insulin ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recombinant DNA technology allows the production of insulin analogues with faster absorption rates from subcutaneous tissue as compared to conventional human regular insulin. We report the time-action profiles of 12 U subcutaneously injected insulin analogues (B9Asp + B27Glu or B10Asp) as evaluated against human regular insulin by means of the euglycaemic clamp technique (blood glucose 5.0 mmol/l) in healthy men. After injection of 12 U of either insulin preparation identical values were found for maximal insulin action (maximal glucose infusion rate, time to peak action), total amount of glucose infused as well as area under the curve of glucose infusion rate. Half-maximal glucose infusion rate was reached significantly earlier after injection of modified insulins (mean ± SD 38 ±7 and 43±5 min) as compared to regular insulin (56 ±14 min, p 〈 0.01). Forty-five min after injection of both insulin analogues glucose infusion rate had increased by 7.4±1.8 or 6.1 ±1.8mg·kg−·min−, reflecting 83 ±27 or 67 ±15% of maximal regular insulin action. In conclusion, the two tested insulin analogues showed similar action profiles, but a significantly faster onset of action as compared to regular insulin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Hyperinsulinaemia ; insulin resistance ; insulin degradation ; haemochromatosis ; cirrhosis ; insulin ; glucagon ; C-peptide ; gastric inhibitory polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study investigated early alterations of glucose metabolism in idiopathic haemochromatosis. Circulating concentrations of glucose, insulin, C-peptide, glucagon, and gastric inhibitory polypeptide (GIF) were measured after a 100-g oral glucose load in 10 men with idiopathic haemochromatosis in the non-cirrhotic stage of the disease. All had normal glucose tolerance and normal body weight. Ten matched healthy subjects were studied as controls. Insulin concentrations increased to significantly higher levels in patients with idiopathic haemochromatosis than in the control subjects from 30 to 180min after the glucose load (p〈0.01), while fasting insulin concentrations were not significantly different (p〉 0.05). Concentrations of glucose, glucagon, C-peptide, and GIF were not significantly different at any time (p〉 0.05). Thus, patients with idiopathic haemochromatosis show hyperinsulinaemia and hence insulin resistance without impaired glucose tolerance in the non-cirrhotic stage. Since pancreatic insulin secretion (C-peptide), glucagon secretion, and the entero-insulinar axis (GIP) are not impaired in these non-cirrhotic patients with idiopathic haemochromatosis, iron accumulation in the hepatocytes may be responsible for the impaired insulin effect and may cause impaired hepatic insulin extraction.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Juvenile type diabetes ; muscular exercise ; blood glucose ; ketosis ; free fatty acids ; amino acids ; insulin ; glucagon ; growth hormone ; cortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metabolic and hormonal effects of muscular exercise were studied in juvenile-type diabetics in relation to the prevailing degree of metabolic control and compared with those in healthy control subjects. Two groups of diabetic patients, one in moderate metabolic control and one in ketosis due to insulin withdrawal, were subjected to a 3 hour bicycle ergometer test of comparable, mild work intensity. In both groups of diabetics the exercise-induced rise in blood lactate was similar, but was significantly higher than in control subjects. Blood alanine levels showed a transient, significant rise in both diabetic groups, but not in controls. Blood concentrations of branch-chained amino acids remained unchanged. In the moderately controlled diabetics, exercise induced a marked fall of blood glucose and increases in blood levels of free fatty acids (FFA), ketone bodies and glucagon, which were comparable to the exercise effects in normal controls. In ketotic diabetics, however, exercise led to an additional rise in blood glucose concentration and to increases in ketone body, glucagon and cortisol levels. Significant correlations were found between the exercise effect on blood glucose and initial blood levels of glucose, FFA, ketone bodies and branch chained amino acids: pre-exercise values of above 325 mg/dl glucose, 1173 μmol/l FFA, 2.13 mmol/l ketone bodies and 0.74 mmol/l branch chained amino acids led to increased blood glucose levels on exercise, whereas below these limits glucose fell during the exercise test. These findings seem to be, at least in part, explained by the hypothesis of a permissive effect of insulin during stimulation of muscle glucose uptake by exercise. The increased circulating levels of glucagon and cortisol during exercise in ketotic diabetics might represent additional hyperglycaemic and, probably more important, lipolytic and ketogenic stimuli. The results suggest that in moderately controlled, non-ketotic diabetics blood glucose falls during exercise; in ketotic, relatively insulin deficient patients, muscular activity has adverse metabolic and hormonal effects: a further increase in blood glucose, plasma glucagon and cortisol and a rapid aggravation of ketosis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 4 (1968), S. 262-267 
    ISSN: 1432-0428
    Keywords: Human adipose tissue ; insulin ; antilipolytic effect ; lipolysis ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les auteurs ont étudié l'effet antilipolytique de l'insuline sur le tissu adipeux humain en utilisant un milieu d'incubation ne contenant pas de glucose. L'activité lipolytique a été mesurée d'après la production de glycérol et d'acides gras libres, et calculée par g de poids humide de tissu. Des coupes de tissu adipeux obtenu à partir de 25 sujets à jeun depuis la veille au soir et n'ayant pas de maladies métaboliques ou endocriniennes, libéraient 0.57 ± 0.20 μmol de glycérol/g de tissu en 2 h, et 2.6 ±0.8 μEq d'acides gras libres/g de tissu en 2 h. La lipolyse était augmentée par addition de 0.01 μg ou plus d'adrénaline ou de noradrénaline par ml, l'augmentation produite par 0.1 ou 1.0 μg de catécholamine/ml étant environ de 100% par rapport au taux de base. Cependant, l'effet de la noradrénaline était significativement plus grand que celui de l'adrénaline. L'addition d'insuline au milieu inhibait la lipolyse. 33 μU d'insuline par ml réduisaient la libération de glycérol à 66± 21 % et la libération d'acides gras libres à 67 ± 24% du taux de base. Une réduction de la lipolyse d'environ 1/3 a été également observée quand la lipolyse était stimulée par 0.1 ou 1.0 μg de catécholamine par ml. La relation effet-dose de l'insuline sur la lipolyse stimulée a été étudiée sur des coupes de tissu adipeux de 14 sujets normaux. Une inhibition significative de la lipolyse a été constatée avec 1.0 μU d'insuline par ml. L'effet lipolytique de 0.1 ou 1.0 μg de catécholamine par ml était complètement inhibé par 100 μU d'insuline par ml. La sensibilité marquée de la lipolyse à l'insuline dans le tissu adipeux humain in vitro serait en accord avec l'idée que la mobilisation des graisses en dépôt dans les conditions physiologiques in vivo est régulée par l'insuline indépendamment du métabolisme du glucose.
    Abstract: Zusammenfassung Am menschlichen Fettgewebein vitro wurde die Hemmung der Lipolyse durch Insulin in glucosefreiem Medium untersucht. Als Parameter der lipolytischen Aktivität wurde die Produktion von Glycerin und freien Fettsäuren bezogen auf Gewebe-Feuchtgewicht gemessen. Die Metabolitfreisetzung durch Fettgewebsschnitte von 25 Normalpersonen betrug in glucosefreiem Medium unter basalen Bedingungen 0.57 ± 0.20 μMol Glycerin/g Gewebe-Feuchtgewicht/2 Std und 2.6 ± 0.8 μEq freie Fettsäuren/g Gewebe-Feuchtgewicht/2 Std — Die Lipolyse wurde durch Zusatz von Noradrenalin oder Adrenalin in Konzentrationen von 0.01 μg/ml oder mehr stimuliert. Bei Konzentrationen von 0.1 und 1.0 μg Katecholamin/ml ergaben sich submaximale Steigerungen der Metabolitfreisetzung auf rund das Doppelte des Basalwertes. Die mit beiden Hormonkonzentrationen erzielten Effekte waren nicht signifikant unterschiedlich, jedoch bei Noradrenalin signifikant größer als bei Adrenalin. — Zusatz von Insulin zum Inkubationsmedium hemmte die Lipolyse. Durch 33 μE Insulin/ml wurde bei Fettgewebsschnitten von 18 Normalpersonen die basale Produktion von Glycerin auf 66 ± 21% und von freien Fettsäuren auf 67 ± 24% reduziert. Auch bei gleichzeitiger submaximaler Stimulation durch Katecholamine betrug die Hemmung der Lipolyse rund 1/3. — Die Konzentration-sabhängigkeit des Insulineffekts auf die Katecholamin-stimulierte Lipolyse wurde an Fettgewebsschnitten von 14 Normalpersonen geprüft. Eine signifikante Lipolyse-hemmung wurde mit einer Konzentration von 1.0 μE Insulin/ml im Inkubationsmedium erzielt. Durch 100 μE/ml wurde die durch Katecholaminzusatz bedingte Stimulation der Lipolyse aufgehoben. — Diein vitro nachweisbare hohe Insulinempfindlichkeit der Lipolyse des menschlichen Fettgewebes läßt darauf schließen, daß die Fettmobilisation auch unter physiologischen Bedingungenin vivo unabhängig vom Glucosestoffwechsel durch Insulin reguliert wird.
    Notes: Summary The antilipolytic effect of insulin on human adipose tissue was studied employing glucose-free incubation medium. The lipolytic activity was measured by the production of glycerol and free fatty acids, and calculated per g wet weight of tissue. Slices of adipose tissue, which was obtained after an overnight fast from 25 subjects selected for lack of metabolic or endocrine diseases, released 0.57 ± 0.20 μmoles glycerol/g tissue/2 h, and 2.6 ± 0.8 μeq. free fatty acids/g tissue/2 h. — Lipolysis was increased by addition of 0.01 or more μg epinephrine or norepinephrine per ml of medium, the increment produced by 0.1 or 1.0 μg catecholamine/ml being about 100% of the basal rate. However, the effect of norepinephrine was significantly greater than the effect of epinephrine. — Addition of insulin to the medium inhibited lipolysis. 33 μU of insulin per ml decreased the release of glycerol to 66 ± 21 % and the release of free fatty acids to 67 ± 24% of the basal rate. A reduction of lipolysis by about 1/3 was also seen when lipolysis was stimulated by 0.1 or 1.0 μg catecholamine per ml. — The dose response of the insulin effect on stimulated lipolysis was studied in slices of adipose tissue from 14 normal subjects. A significant inhibition of lipolysis was demonstrated with 1.0 μU of insulin per ml. The lipolytic effect of 0.1 or 1.0 μg catecholamine per ml was completely inhibited by 100 μU insulin per ml. — The marked insulin sensitivity of lipolysis in human adipose tissuein vitro would be in agreement with the concept, that mobilization of depot fat under physiological conditionsin vivo is regulated by insulin, independent of glucose metabolism.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1335
    Keywords: Antineoplastic efficacy ; Melphalan ; Diazoxide ; Insulin ; Mammary carcinoma ; Sprague-Dawley rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anticancer activity of melphalan andN-(2-chloroethyl)-N-nitrosocarbamoyl-ω-lysine (CNC-ω-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-ω-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-ω-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (〈20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Vitamins A, E ; Semisynthetic fatty diet ; Methylnitrosourea ; Mammary carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than four-fold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 116 (1990), S. 538-549 
    ISSN: 1432-1335
    Keywords: Androgen-linked alkylating agents ; Methylnitrosourea ; Mammary carcinoma ; Anticancer activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This article gives a comprehensive survey on the anticancer activity of nitrosoureas linked to steroidal androgens in methylnitrosourea (MMU)-induced rat mammary carcinoma. cis-Androsterone, testosterone, 19-nortestosterone and 5-α-dihydrotestosterone were used as carrier hormones and were linked to various cytotoxic N-[N′-(2-chloroethyl)-N′-nitrosocarbamoyl] (CNC)-aminoacids and to N-(2-hydroxyethyl)-N′-(2-chloroethyl)-N′-nitrosourea hemisuccinate (HECNU-hemisuccinate). In the MNU-model used esters of dihydrotestosterone (DHT) invariably were more active and less toxic than those of testosterone, nortestosterone and cis-androsterone. Within the DHT esters of CNC-aminoacids those of CNC-glycine, CNC-methionine and CNC-alanine showed the highest antineoplastic activities and superiority compared with equimolar dosages of their unlinked mixtures. Additionally, CNC-alanine-DHT ester had the highest therapeutic ratio of all agents investigated. HECNU-hemisuccinate-DHT ester, on the other hand, achieved even higher antitumor activity at the optimal dose but had a narrower therapeutic ratio. No obvious correlation between antineoplastic efficacy and receptor binding affinity could be demonstrated, but, to be active, a conjugate apparently had to have some receptor binding affinity for both androgen and progesterone receptors. The results obtained indicate that linking antineoplastic agents to transport molecules with affinity to steroid receptors is a highly promising approach to obtain drugs with specific activity in steroid receptor containing tumors.
    Type of Medium: Electronic Resource
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